Norditropin

INDICATIONS

Pediatric Patients

Norditropin [somatropin (rDNA origin) injection] is
indicated for the treatment of pediatric patients with growth failure due to inadequate secretion of endogenousgrowth hormone (GH).

Norditropin [somatropin (rDNA
origin) injection] is indicated for the treatment of pediatric patients with
short stature associated with Noonan syndrome.

Norditropin [somatropin (rDNA
origin) injection] is indicated for the treatment of pediatric patients with
short stature associated with Turner syndrome.

Norditropin [somatropin (rDNA origin)
injection] is indicated for the treatment of pediatric patients with short
stature born small for gestational age (SGA) with no catch-up growth by age 2
to 4 years.

Adult Patients

Norditropin [somatropin (rDNA
origin) injection] is indicated for the replacement of endogenous GH in adults
with growth hormone deficiency (GHD) who meet either of the following two
criteria:

Adult Onset (AO): Patients who have GHD, either alone or
associated with multiple hormone deficiencies (hypopituitarism), as a result of
pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma;
or

Childhood Onset (CO): Patients who were GH deficient
during childhood as a result of congenital, genetic, acquired, or idiopathic causes.

Patients who were treated with
somatropin for GHD in childhood and whose epiphyses are closed should be
reevaluated before continuation of somatropin therapy at the reduced dose level
recommended for GHD adults. According to current standards, confirmation of the
diagnosis of adult GHD in both groups involves an appropriate growth hormone
provocative test with two exceptions: (1) patients with multiple other
pituitary hormone deficiencies due to organic disease; and (2) patients with
congenital/genetic growth hormone deficiency.

DOSAGE AND ADMINISTRATION

For subcutaneous injection. Therapy with Norditropin
should be supervised by a physician who is experienced in the diagnosis and
management of pediatric patients with short stature associated with GHD, Noonan
syndrome, Turner syndrome or SGA, and adult patients with either childhood
onset or adult onset GHD.

Dosing Of Pediatric Patients

General Pediatric Dosing Information

The Norditropin dosage and administration schedule should
be individualized based on the growth response of each patient. Serum insulin-like
growth factor I (IGF-I) levels may be useful during dose titration.

Response to somatropin therapy in pediatric patients
tends to decrease with time. However, in pediatric patients, the failure to
increase growth rate, particularly during the first year of therapy, indicates
the need for close assessment of compliance and evaluation for other causes of
growth failure, such as hypothyroidism, undernutrition, advanced bone age and
antibodies to recombinant human GH (rhGH).

Treatment with Norditropin for short stature should be
discontinued when the epiphyses are fused.

Pediatric Growth Hormone Deficiency (GHD)

A dosage of 0.024 to 0.034 mg/kg/day, 6 to 7 times a
week, is recommended.

Pediatric Patients with Short Stature Associated with
Noonan Syndrome

Not all patients with Noonan syndrome have short stature;
some will achieve a normal adult height without treatment. Therefore, prior to
initiating Norditropin for a patient with Noonan syndrome, establish that the
patient does have short stature. A dosage of up to 0.066 mg/kg/day is
recommended.

Pediatric Patients with Short Stature Associated with
Turner Syndrome

A dosage of up to 0.067 mg/kg/day is recommended.

Pediatric Patients with Short Stature Born Small for
Gestational Age (SGA) with No Catch-up Growth by Age 2 to 4 Years

A dosage of up to 0.067 mg/kg/day is recommended.

Recent literature has recommended initial treatment with
larger doses of somatropin (e.g., 0.067 mg/kg/day), especially in very short
children (i.e., HSDS < -3), and/or older/pubertal children, and that a
reduction in dosage (e.g., gradually towards 0.033 mg/kg/day) should be
considered if substantial catch-up growth is observed during the first few
years of therapy. On the other hand, in younger SGA children (e.g.,
approximately < 4 years) (who respond the best in general) with less severe
short stature (i.e., baseline HSDS values between -2 and -3), consideration
should be given to initiating treatment at a lower dose (e.g., 0.033
mg/kg/day), and titrating the dose as needed over time. In all children,
clinicians should carefully monitor the growth response, and adjust the rhGH
dose as necessary.

Dosing Of Adult Patients

Adult Growth Hormone Deficiency (GHD)

Either of two approaches to Norditropin dosing may be
followed: a non-weight-based regimen or a weight-based regimen.

Non-weight based — based on published consensus
guidelines, a starting dose of approximately 0.2 mg/day (range, 0.15-0.30
mg/day) may be used without consideration of body weight. This dose can be
increased gradually every 1 to 2 months by increments of approximately 0.1-0.2
mg/day, according to individual patient requirements based on the clinical
response and serum insulin-like growth factor I (IGF-I) concentrations. The
dose should be decreased as necessary on the basis of adverse events and/or
serum IGF-I concentrations above the age-and gender-specific normal range.
Maintenance dosages vary considerably from person to person, and between male
and female patients.

Weight-based — based on the dosing regimen used in
the original adult GHD registration trials, the recommended dosage at the start
of treatment is not more than 0.004 mg/kg/day. The dose may be increased to not
more than 0.016 mg/kg/day after approximately 6 weeks according to individual
patient requirements. Clinical response, side effects, and determination of
age-and gender-adjusted serum IGF-I concentrations should be used as guidance
in dose titration.

A lower starting dose and smaller dose increments should
be considered for older patients, who are more prone to the adverse effects of
somatropin than younger individuals. In addition, obese individuals are more
likely to manifest adverse effects when treated with a weight-based regimen. In
order to reach the defined treatment goal, estrogen-replete women may need
higher doses than men. Oral estrogen administration may increase the dose
requirements in women.

Preparation And Administration

Norditropin® FlexPro® 5 mg/1.5 mL,
10 mg/1.5 mL and 15 mg/1.5 mL:

Instructions for delivering the dosage are provided in
the PATIENT INFORMATION and INSTRUCTIONS FOR USE leaflets enclosed with the
Norditropin FlexPro prefilled pen.

Norditropin NordiFlex® 30 mg/3 mL:

Instructions for delivering the dosage are provided in
the PATIENT INFORMATION and INSTRUCTIONS FOR USE leaflets enclosed with the
Norditropin NordiFlex prefilled pen.

Parenteral drug products should always be inspected
visually for particulate matter and discoloration prior to administration,
whenever solution and container permit. Norditropin MUST NOT BE INJECTED if the
solution is cloudy or contains particulate matter. Use it only if it is clear
and colorless.

Injection sites should always be rotated to avoid
lipoatrophy.

HOW SUPPLIED

Dosage Forms And Strengths

Norditropin is available preloaded in the Norditropin
FlexPro or Norditropin NordiFlex pens:

Unused Norditropin FlexPro and
NordiFlex prefilled pens must be stored at 2°C-8°C/36°F-46°F (refrigerator). Do
not freeze.

Avoid direct light. After the
initial injection, a Norditropin FlexPro or NordiFlex prefilled pen may be EITHER
stored in the refrigerator (2°C-8°C/36°F-46°F) and used within 4 weeks OR
stored for up to 3 weeks at room temperature not more than 25°C (77°F). Discard
unused portion.